In this large study of GDM in Chinese women, advanced maternal age, pre-pregnancy overweight or obesity and family history of diabetes were confirmed to be risk factors. In addition, a history of recurrent vulvovaginal candidiasis or spontaneous abortion and residency in south China appeared to be novel risk factors in this population.
The prevalence of macrosomia varied dramatically between different areas of China. High pre-pregnancy BMI and GWG represent main modifiable risk factors for macrosomia and need more attention from health care providers.
Inflammation is a hallmark of several disease states ranging from neurodegeneration to sepsis but is also implicated in physiological processes like ageing. Non-resolving inflammation and prolonged neuroinflammation are unclear processes implicated in several conditions, including ageing. In this study we studied the long-term effects of endotoxemia, as systemic lipopolysaccharide (LPS) injection, focusing on the role of astrocyte activation and cytokine release in the brain of aged rats. A single dose of LPS (2 mg/kg) or 0.9% saline was injected intraperitoneally in aged rats. Levels of pro-inflammatory cytokines (TNFα and IL-1β) and NF-κB p65 activation were measured systemically and in hippocampal tissue. Astrocytes and cytokines release in the CNS were detected via double immunofluorescence staining at different time-points up to day 30. Serum levels of TNFα and IL-1β were significantly increased acutely after 30 minutes (p<0.001) and up to 6 hours (p<0.001) following LPS-injection. Centrally, LPS-treated rats showed up-regulated mRNA expression and protein levels of pro-inflammatory cytokines in the hippocampus. These changes associated with astrogliosis in the hippocampus dentate gyrus (DG), IL-1β immunoreactivity and elevated NF-κB p65 expression up to day 30 post LPS exposure. Overall, these data demonstrate that LPS induces prolonged neuroinflammation and astrocyte activation in the hippocampus of aged rats. Hippocampal NF-κB p65 and excessive astrocytes-derived IL-1β release may play a pivotal role in regulating long-lasting neuroinflammation.
Modulation of autophagy has been increasingly regarded as a promising cancer therapeutic approach. In this study, we screened several ginsenosides extracted from Panax ginseng and identified ginsenoside Ro (Ro) as a novel autophagy inhibitor. Ro blocked the autophagosome-lysosome fusion process by raising lysosomal pH and attenuating lysosomal cathepsin activity, resulting in the accumulation of the autophagosome marker MAP1LC3B/LC3B and SQSTM1/p62 (sequestosome 1) in various esophageal cancer cell lines. More detailed studies demonstrated that Ro activated ESR2 (estrogen receptor 2), which led to the activation of NCF1/p47(PHOX) (neutrophil cytosolic factor 1), a subunit of NADPH oxidase, and subsequent reactive oxygen species (ROS) production. Treatment with siRNAs or inhibitors of the ESR2-NCF1-ROS axis, such as N-acetyl-L-cysteine (NAC), diphenyleneiodonium chloride (DPI), apocynin (ACN), Tiron, and Fulvestrant apparently decreased Ro-induced LC3B-II, GFP-LC3B puncta, and SQSTM1, indicating that ROS instigates autophagic flux inhibition triggered by Ro. More importantly, suppression of autophagy by Ro sensitized 5-fluorouracil (5-Fu)-induced cell death in chemoresistant esophageal cancer cells. 5-Fu induced prosurvival autophagy, and by inhibiting such autophagy, siRNAs against BECN1/beclin 1, ATG5, ATG7, and LC3B enhanced 5-Fu-induced autophagy-associated and apoptosis-independent cell death. We observed that Ro potentiates 5-Fu cytotoxicity via delaying CHEK1 (checkpoint kinase 1) degradation and downregulating DNA replication process, resulting in the delayed DNA repair and the accumulation of DNA damage. In summary, these data suggest that Ro is a novel autophagy inhibitor and could function as a potent anticancer agent in combination therapy to overcome chemoresistance.
OBJECTIVETo evaluate the usefulness of a fasting plasma glucose (FPG) at 24–28 weeks’ gestation to screen for gestational diabetes mellitus (GDM).RESEARCH DESIGN AND METHODSThe medical records and results of a 75-g 2-h oral glucose tolerance test (OGTT) of 24,854 pregnant women without known pre-GDM attending prenatal clinics in 15 hospitals in China were examined.RESULTSFPG cutoff value of 5.1 mmol/L identified 3,149 (12.1%) pregnant women with GDM. FPG cutoff value of 4.4 mmol/L ruled out GDM in 15,369 (38.2%) women. With use of this cutoff point, 12.2% of patients with mild GDM will be missed. The positive predictive value is 0.322, and the negative predictive value is 0.928.CONCLUSIONSFPG at 24–28 weeks’ gestation could be used as a screening test to identify GDM patients in low-resource regions. Women with an FPG between ≥4.4 and ≤5.0 mmol/L would require a 75-g OGTT to diagnose GDM. This would help to avoid approximately one-half (50.3%) of the formal 75-g OGTTs in China.
Objective: To determine associations between lipid profiles in early pregnancy stratified by body mass index (BMI) and risk of developing gestational diabetes mellitus (GDM). Study Design: A total of 2488 healthy pregnant women were enrolled prospectively. Fasting plasma lipid profiles were measured at mean 11 weeks of gestation including triglycerides (TGs), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and cholesterol (CHO). We assessed early pregnancy maternal lipid concentrations in different tertiles in association with the risk of GDM stratified for BMI. Multivariable logistic regression analyses were used to estimate the relative risk of GDM by calculating odds ratios and 95% confidence intervals (CIs). Results: In univariate analyses, pregnant women with GDM had significantly increased serum TG, CHO, LDL concentrations, LDL/HDL ratio, and decreased LDL concentrations, compared to control groups, each P < .01, respectively. After adjustment for confounders, there was a 1.8-fold increase in risk for GDM in the lean group (95% CI: 1.2-2.7) and 2.7-fold increase in the obese group (95% CI: 1.1-6.6), respectively, if TG 1.58 mmol/L. About a 50% decrease in the risk of GDM was observed in lean women with HDL 2.22 mmol/L (95% CI: 0.3-0.9). No significant correlations of other lipid profiles with the risk of developing GDM were observed. Conclusion: Early pregnancy dyslipidemia is associated with the risk of developing GDM. Lean or obese women with higher TG concentrations are at an increased risk for developing GDM while lean women with high HDL are protected.
Background and Purpose-We conducted this randomized controlled trial to investigate the effects of therapeutic hypothermia on mortality and neurological outcome in patients with massive cerebral hemispheric infarction. Methods-Patients within 48 hours of symptom onset were randomized to either a hypothermia group or a control group.Patients in the hypothermia group were given standard medical treatment plus endovascular hypothermia with a target temperature of 33 or 34°C. Hypothermia was maintained for a minimum of 24 hours. Patients in the control group were given standard medical treatment only with a target temperature of normothermia. The primary end points were mortality and the modified Rankin Scale score at 6 months. Results-There were 16 patients in the hypothermia group and 17 patients in the control group. At 6 months, 8 patients had died in the hypothermia group versus 7 patients in the control group (P=0.732). The main cause of death was fatal herniation caused by a pronounced rise in intracranial pressure. Seven patients (43.8%) had a modified Rankin Scale of 1 to 3 in the hypothermia group versus 4 patients (23.5%) in the control group (P=0.282). Additionally, of the survivors, patients in the hypothermia group achieved better neurological outcomes compared with those in the control group (7/8, 87.5% versus 4/10, 40.0%; P=0.066; odds ratio=10.5; 95% confidence interval, 0.9-121.4).
Conclusions-Mild
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